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溶菌酶基因表現之調控機制
Regulation mechanism of lysozyme gene expression
摘要
溶菌酶是一種在原核、真核生物均中表現的酵素，其功能在分解細菌的細胞壁，可以幫助宿主對抗細菌的感染。溶菌酶主要表現在髓系（myeloid lineages）及輸卵管細胞中，是具有組織專一性表現的基因。溶菌酶基因中隨著髓系細胞自然分化的過程由低表現到大量表現。在活體外，髓系細胞可經由phorbol 12-myristate 13-acetate（PMA）刺激成為單核球，進一步被細菌內毒素活性根源的脂多醣（lipopolysaccharide,LPS）刺激成為巨噬細胞，此時巨噬細胞之溶菌酶基因也中大量表現，而製造出溶菌酶。溶菌酶基因的表現中隨著髓系細胞的分化，逐步受到調控。溶菌酶基因在巨噬細胞的大量表現，需有調控序列及轉錄因子參與調控。調控序列包含啟動子與-6.1 kb E、-3.9 kb E、-2.7 kb E加強子以及-2.4 kb的靜默子。NF-I（nuclear factor I）、CBP因子（cyclic AMP response element binding protein）、SP1（specific protein 1）、C/EBP（CCAAT/enhancer-binding proteins）、PU.1（purine-rich box binding protein, also called SPI1）均為重要的轉錄因子。溶菌酶基因表現的調控是探討基因調控極佳的模式。本文就前人及相關研究結果進行綜合性討論，並分析不同溶菌酶的序列，期能有助於吾人對溶菌酶基因之調控機制更深入的了解。
並列摘要
Lysozyme expresses both in prokaryotes and eukaryotes. The lysozyme gene encodes an enzyme which can damage bacterial cell walls. The cleavage-bacterial-wall function is a nature form of protection from bacterial infection. Lysozyme is a tissue-specific gene which mainly expresses in myeloid lineage and oviduct cells. During myelopoiesis to macrophages, lysozyme transcripts express from detectable level to its maximal level. Myeloid cells can be differentiated into monocytes by treatment with phorbol 12-myristate 13-acetate (PMA), and can be further differentiated into macrophages by lipopolysaccharide (LPS is found in the membrane of bacteria, and acts as endotoxins.) in vitro. The transcription of lysozyme reaches its maximal level in mature, activated macrophages. During the process when the myeloid progenitor differentiates into macrophages, the expression of lysozyme transcript is regulated step by step. The regulation of lysozyme gene expression needs the recruitment of regulatory sequence and transcription factors. The transcription is regulated by the following five cis-regulatory elements: a promoter, three enhancers situated -6.1 kb, -3.9 kb, and -2.7 kb upstream of the transcription start site, and a silencer element at -2.4 kb. The transcription factors of NF-I (nuclear factor I) 、 CBP(cyclic AMP response element binding protein)、 SP1(specific protein 1)、 C/EBP(CCAAT/enhancer-binding proteins)、 PU.1(purine-rich box binding protein, also called SPI1) involve in the gene expression. The regulation of lysozyme gene expression is a good model for the study of gene regulation. Present report focuses on a more in-depth understanding of lysozyme gene regulation in animals. Providing further information relative to the lysozyme gene regulation is expected.